Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Polysorbates”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 433 records · Page 24Linked to original sources
PubMed2002

Inverse relationship of protein concentration and aggregation.

PURPOSE: To determine the effect of protein concentration on aggregation induced through quiescent shelf-life incubation or shipping-related agitation. METHODS: All aggregation was measured by size-exclusion high-performance liquid chromatography. Aggregation was induced by time-dependent incubation under stationary conditions or by agitation caused by shaking, vortexing, or vibration using simulated shipping conditions. RESULTS: Protein aggregation is commonly a second- or higher-order process that is expected to increase with higher protein concentration. As expected, for three proteins (PEG-GCSF, PEG-MGDF, and OPG-Fc) that were examined, the aggregation increased with higher protein concentration if incubated in a quiescent shelf-life setting. However, aggregation decreased with higher protein concentration if induced by an air/water interface as a result of agitation. This unexpected result may be explained by the rate-limiting effect on aggregation of the air/water interface and the critical nature of the air/ water interface to protein ratio that is greatest with decreased protein concentration. The non-ionic detergent polysorbate 20 enhanced the aggregation observed in the quiescently incubated sample but abrogated the aggregation induced by the air/water interface. CONCLUSIONS: The effect of protein concentration was opposite for aggregation that resulted from quiescent shelf-life treatment compared to induction by agitation. For motionless shelf-life incubation, increased concentration of protein resulted in more aggregation. However, exposure to agitation resulted in more aggregation with decreased protein concentration. These results highlight an unexpected complexity of protein aggregation reactions.

Dose-Response Relationship, Drug↗
PubMed2004

Amphiphilogels for drug delivery: formulation and characterization.

PURPOSE: This study examines the microstructure, gelation temperatures, and flow properties of novel amphiphilogels consisting solely of non-ionic surfactants. METHODS: Gels were prepared by mixing the solid gelator (sorbitan monostearate or sorbitan monopalmitate) and the liquid phase (liquid sorbitan esters or polysorbates) and heating them at 60 degrees C to form a clear isotropic sol phase, and cooling the sol phase to form an opaque semisolid at room temperature. Gel microstructure was examined by light and electron microscopy and by small angle neutron scattering (SANS); gelation temperatures were measured by hotstage microscopy, a melting point apparatus, and high sensitivity differential scanning calorimetry (HSDSC). Flow rheograms were performed to establish the zero-rate viscosity of the gels and their performance under shear. RESULTS: Gel microstructures consisted mainly of clusters of tubules of gelator molecules that had aggregated upon cooling of the sol phase, forming a 3D network throughout the continuous phase. The gels demonstrated thermoreversibility. Gelation temperature and viscosity increased with increasing gelator concentration, indicating a more robust gel network. At temperatures near the skin surface temperature, the gels softened considerably; this would allow topical application. CONCLUSIONS: This study has demonstrated the formation/preparation of stable, thermoreversible, thixtropic surfactant gels (amphiphilogels) with suitable physical properties for topical use.

Administration, Topical↗
PubMed2003

Effect of manufacturing process parameters on virus inactivation by solvent-detergent treatment in a high-purity factor IX concentrate.

BACKGROUND AND OBJECTIVES: Treatment with solvent-detergent is widely used for ensuring the virus safety of plasma products. Laboratory studies have shown this procedure to be effective for inactivating enveloped viruses under manufacturing conditions. In the present study, the effect of different manufacturing process parameters on virus inactivation by treatment with polysorbate 80 and tri-n-butyl phosphate were investigated for a high-purity factor IX concentrate in order to evaluate the robustness of this step. MATERIALS AND METHODS: Samples of factor IX intermediate were obtained, virus was added and the kinetics of virus inactivation followed during incubation. The effect of altering the conditions on virus inactivation was tested. RESULTS: Solvent-detergent treatment was confirmed to effectively inactivate, i.e. by > or = 5 log, a wide range of representative enveloped viruses under standard conditions. Virus inactivation was consistently effective in a number of different manufacturing batches. Of the parameters tested, only solvent-detergent concentration and temperature significantly effected virus inactivation. CONCLUSIONS: The robustness of the solvent-detergent step for virus inactivation has been confirmed. Using the data generated, appropriate limits can be set for this manufacturing process step.

Detergents↗
PubMed1999

Peroral polypeptide delivery. A comparative in vitro study of mucolytic agents.

Besides the absorption and enzymatic barrier, the diffusion barrier based on the mucus gel layer covering gastrointestinal (GI) epithelia represents the third major factor being responsible for a very poor bioavailability of orally administered (poly)peptide drugs. In order to overcome the latter ones, the mucus liquefying action of various types of mucolytic agents and their influence on the model polypeptide drug insulin has been evaluated in a comparative in vitro study. The results demonstrated that the proteases pronase (EC 3.4.24.31) and papain (EC 3.4.22.2) cause a relative reduction in mucus viscosity of 75.9 +/- 6.8% and 51.1 +/- 3.3% (n = 3) after 6 h of incubation at pH 5.0, respectively, whereas the mucolytic effect of the detergents Triton X-100 (octoxinol) and Tween 20 (polysorbate 20) was markedly lower. Mucolytic proteases and well established mucolytic sulfhydryl compounds, however, caused a rapid degradation of insulin. Therefore these two types of mucolytic agents can only be used if the (poly)peptide drug proves stable towards degradation. The results indicate the strict need of novel mucolytic agents for the peroral administration of therapeutic (poly)peptides.

Animals↗
PubMedDate not supplied

Long-term stability of PBCA nanoparticle suspensions.

In this study, the stability of poly(butyl cyanoacrylate) (PBCA) nanoparticle suspensions was examined for up to 1 year by measuring the nanoparticle sizes. The nanoparticles were prepared with different stabilizers (dextran 70.000, poloxamer 188, or polysorbate 85), and the particle size was determined before and after purification by centrifugation and after dilution with different solutions (0.1 N HCl, 0.01 N HCl, H2O, and PBS). The most constant sizes were with the untreated acidic nanoparticle suspensions. In all other cases, agglomeration of the particles occurred: the extent of this agglomeration and the time at which the agglomeration occurred depended on the experimental conditions. Nanoparticle polymer degradation, as indicated by size decrease, was not observed. Thus, PBCA nanoparticles can be stored as suspensions, making the lyophilization and the sometimes problematic resuspension by ultrasonication, unnecessary, which is advantageous for clinical applications.

Capsules↗
PubMed1999

Effects of surfactant on release characteristics of clonidine hydrochloride from ethylcellulose film.

The effects of Tween 80 (polysorbate 80) and Span 80 (sorbitan monooleate) surfactants on release characteristics of clonidine hydrochloride from ethylcellulose 10 and 20 cps matrix films containing castor oil as a plasticizer were investigated. The release rates of drug from these films in water at 37 degrees C were found to increase with the addition of surfactant, which was highest for the film prepared from ethylcellulose 20 cps with Tween 80. The experimental values of the cumulative amount of drug released were found to conform to the solution matrix model. The calculated values of the cumulative amount of clonidine hydrochloride released using the experimentally determined diffusion coefficients were also found to be in good agreement with the observed values.

Algorithms↗
PubMed2003

Commonly used numbers of microspheres affect cardiac vascular resistance.

The main goal of the study was to examine how the microsphere technique affects the hemodynamics and mitochondrial energy status of the Langendorff-perfused rat heart. The hearts were perfused at a constant flow with Tyrode solution. NADH videofluorometry of the surface of the left ventricle was used to record the mitochondrial energy status as indication of regional ischemia. The effects of seven successive (separated by 10 min) injections of 0.1 ml of saline or (0.05% Tween 20; polysorbate 20, Sigma-Aldrich, St. Louis, MO, U.S.A.) or (0.05% Tween 20 + microspheres) were studied. The number of microspheres per injection were: #1 (2,500), #2 (5,000), #3 (10,000), #4 (20,000), #5 (40,000), #6 (40000), and #7 (80000). The anti-aggregation agent Tween always caused a biphasic response in perfusion pressure. Compared with the Tween effect, the injection of microspheres caused an initial change (mm Hg) in perfusion pressure of #1 (-10), #2 (NS), #3 (NS), #4 (+7.5), #5 (+12.3), #6 (+14.4), #7 (+18.3), and a delayed change (10 min after injection) of #1 (-22.2), #2 (-6.0), #3 (-4.1), #4 (-4.5), #5 (NS), #6 (NS), and #7 (+5.9). The microspheres caused a significant delayed increase in NADH only for injection #6 and #7. Similar results were found for different durations of the input function or when hearts were perfused at constant perfusion pressure. In hearts without flow reserve (10 microM adenosine), Tween injections were without effect, whereas three successive injections of 60,000 microspheres each only caused increases in perfusion pressure and NADH. The data demonstrate that in hearts with flow reserve present, even very low numbers of microspheres (2,000/g heart) cause large decreases in perfusion pressure without obvious signs of ischemia. When flow reserve was exhausted by either microsphere loading or adenosine addition, microspheres only caused increases in perfusion pressure and resulted in detectable ischemia (NADH). It is concluded that microspheres affect the vascular resistance of the heart and that these effects are flow reserve dependent.

Animals↗
PubMed1980

Management of hot tar burns.

Burns due to hot tar present a difficult management problem because the tar is difficult to remove without inflicting further injury to the underlying burn. We have found the surface active agent polyoxyethylene sorbitan (Tween 80, Sigma, St. Louis, MO) or Polysorbate (Sigma), by itself or in combination with an antibiotic ointment (neomycin sulfate) to be a safe and effective means of tar removal.

Adult↗
PubMed2005

Reducing surface tension in endodontic chelator solutions has no effect on their ability to remove calcium from instrumented root canals.

The aim of this study was to evaluate the effect of reducing surface tension in endodontic chelator solutions on their ability to remove calcium from instrumented root canals. Aqueous solutions containing 15.5% EDTA, 10% citric acid, or 18% 1- hydroxyethylidene-1, 1-bisphosphonate (HEBP) were prepared with and without 1% (wt/wt) polysorbate (Tween) 80 and 9% propylene glycol. Surface tension in these solutions was measured using the Wilhelmy method. Sixty-four extracted, single-rooted human teeth of similar length were instrumented and irrigated with a 1% sodium hypochlorite solution and then randomly assigned (n = 8 per group) to receive a final one-minute rinse with 5 ml of test solutions, water, or the pure aqueous Tween/propylene glycol solution. Calcium concentration in eluates was measured using atomic absorption spectrometry. Incorporation of wetting agents resulted in a reduction of surface tension values by approximately 50% in all tested solutions. However, none of the solutions with reduced surface tension chelated more calcium from canals than their pure counterparts (p > 0.05).

Analysis of Variance↗
PubMed2006

PS80 interferes with the antiallergic effect of Cry-consensus peptide, a novel recombinant peptide for immunotherapy of Japanese cedar pollinosis, at very low concentration through modulation of Th1/Th2 balance.

Polysorbate 80 (PS80 or Tween-80) is often used as an additive to promote the rapid solubilization of pharmaceuticals in aqueous solutions. We investigated whether coinjection of a minimal amount of PS80 had a modulatory effect on the immunotherapeutic effects of Cry (Cryptomeria)-consensus peptide, a novel peptide developed for the therapeutic management of Japanese cedar pollinosis, using a Cry j 1-sensitized mouse model with experimental allergic rhinitis. Subcutaneous challenge with Cry-consensus peptide plus 50 microg/ml of PS80 did not affect the antigen-specific proliferation of splenocytes, but decreased the potency of Cry-consensus peptide to inhibit antigen-specific interleukin (IL)-5 production by the cells significantly in comparison with challenge with Cry-consensus peptide alone. However, there was no significant difference between the effect of Cry-consensus peptide administration on interferon (IFN)-gamma production in the presence and absence of PS80, indicating that PS80 interfered with the T helper 1 (Th1)-dominant T helper balance induced by Cry-consensus peptide challenge. Moreover, the increase in the level of antigen-specific immunoglobulin G2a (IgG2a) induced by Cry-consensus peptide challenge was inhibited slightly but unambiguously by PS80 coinjection. These in vitro experiments indicated that PS80 induces Th2-type differentiation of T helper cells through preferential inhibition of IFN-gamma expression relative to IL-5 expression in splenocytes in a concentration-dependent manner. In naïve mice, sensitization by Cry-consensus peptide with PS80 induced antigen-specific IL-5 production more potently than sensitization by Cry-consensus peptide alone, and when PS80 was added to bone marrow-derived dendritic cells, the endocytosis of fluorescence-labelled Cry-consensus peptide was dramatically inhibited in a concentration-dependent manner. Therefore, we conclude that PS80 has an immunomodulatory effect on the antigen-specific response resulting in a shift towards Th2 predominance with respect to the antigen recognition stage. Taken together, our findings suggest that PS80 might decrease the efficacy of Cry-consensus peptide through modulation of the efficiency of antigen endocytosis and/or of the direction of successive T helper cell differentiation.

Allergens↗
PubMed2004

A rapid method for the evaluation of both extrinsic and intrinsic contamination and resulting spoilage of water-in-oil emulsions.

AIMS: To develop a method for studying the microbial spoilage of water-in-oil emulsions and to use this to investigate (i) the intrinsic stability of water-in-oil formulations and (ii) Pseudomonas aeruginosa SP1-induced spoilage of a proprietary emulsion. METHODS AND RESULTS: Aliquots of test emulsion were placed into wells of a microtitre plate and the opacity (492 nm) monitored at 120-min intervals over several hours. Cracking of the emulsion was associated with marked reductions in opacity. Rate and extent of change in O.D. could be used as indicators of spoilage. Spoilage of a laboratory emulsion formulation was investigated where microorganisms with demonstrated spoilage potential were incorporated either into the water phase prior to emulsification or where the proportion of contaminated water droplets was varied by dilution of contaminated emulsion with a sterile formulation. Results suggested that the route of introduction was a critical determinant of the probability of gross spoilage. Ps. aeruginosa SP1-induced spoilage of a proprietary formulation was found to be independent of growth in the formulation; rather it was attributed to the presence of a heat-labile extracellular spoilage-factor that was protease labile and possessed both lipase and polysorbate hydrolytic activity. Such spoilage potential was unique to one Ps. aeruginosa culture filtrate amongst five pseudomonads tested. SIGNIFICANCE AND IMPACT OF THE STUDY: The method is both rapid and reproducible, enables evaluation of the effects of route of contamination upon emulsion spoilage and has potential application in formulation development for cosmetic, pharmaceutical and food products.

Colony Count, Microbial↗
PubMed1986

The plasto-elasticity and compressibility of coated powders and the tensile strengths of their tablets.

A study has been made of the effects produced on the tensile strength, brittle fracture index (BFI), 'plasto-elasticity' ratio, ER/PC, and yield pressure (1/KH derived from Heckel plots) of sodium salicylate and calcium carbonate as a result of coating their particles with increasing amounts of silicones and polysorbates before subjecting them to compression to form tablets. The coatings act as lubricants reducing bond formation due to plastic deformation of particles. They caused a reduction in the tensile strengths and yield pressures of the tablets but increased their BFI values and their ER/PC ratios. Tablets of calcium carbonate tended to cap or laminate when their BFI value was greater than 0.7 and their ER/PC ratio was greater than 7. Sodium salicylate whose BFI values were all less than 0.7 produced satisfactory tablets when their ER/PC ratio was less than 10 but tended to cap or laminate when it was greater than 10.

Calcium Carbonate↗
PubMed1978

Protein-free and low-protein media for the cultivation of Leptospira.

A protein-free medium composed of charcoal-detoxified Tweens (polysorbates), vitamins B12 and B1, inorganic salts, and organic buffer is described that supports the growth and subculture of pathogenic and saprophytic Leptospira. Growth was initiated from small inocula, and cell densities of 10(9) organisms per ml were attained. Antigenicity and immunogenicity of Leptospira cultivated in this medium were similar to those of cells cultivated in serum-containing media. The protein-free medium was converted to a low-protein medium by the addition of 0.1% bovine serum albumin.

Antigens, Bacterial↗
PubMed1986

Gellan gum as a substitute for agar in leptospiral media.

An albumin polysorbate semisolid medium (Ellinghausen McCullough Johnson Harris medium) gelled with gellan gum (Gelrite; Kelco Div., Merck & Co., Inc.) compared favorably with conventional agar media for the cultivation of both pathogenic and saprophytic leptospires. The gellan gum medium supported the growth of all 18 leptospiral strains studied which included an array of serovars with various fastidious growth characteristics. Gellan gum medium was also used advantageously as a long-term maintenance medium; 9- to 12-month-old cultures still contained viable organisms. The colonial growth in gellan gum plating medium of six representative strains was consistent with previously described colonial growth on agar plating media. In addition, gellan gum medium appeared to be an excellent medium for the recovery of leptospires from the blood, liver, and kidneys of hamsters experimentally infected with a virulent Leptospira interrogans serovar bataviae strain. As few as 1 to 10 organisms in the infective tissue could be recovered in semisolid Ellinghausen McCullough Johnson Harris-gellan gum medium. The antigenicity did not appear to be affected by growth in gellan gum medium. The hamster-virulent strain of L. interrogans serovar bataviae isolated from a moribund hamster maintained its virulence after 10 sequential passages in gellan gum medium. Gellan gum medium can be a valuable adjunct to currently used cultural procedures.

Agar↗
PubMed2004

Taxane-mediated antiangiogenesis in vitro: influence of formulation vehicles and binding proteins.

Paclitaxel (Taxol) and docetaxel (Taxotere) have been shown to inhibit angiogenesis at low concentrations that do not affect cancer cell proliferation. Here, we used rat aortic rings and human umbilical vein endothelial cells to evaluate the influence of their formulation vehicles Cremophor EL and polysorbate 80, as well as serum binding proteins on taxane-mediated antiangiogenesis. The data show that clinically relevant concentrations of the vehicles and binding proteins nullify the antiangiogenic activity of both taxanes. It is suggested that these agents may need to be used at much higher doses than anticipated for effective antiangiogenic chemotherapy.

Angiogenesis Inhibitors↗
PubMed1983

Drug prevention of blood-aqueous barrier disruption.

In order to evaluate the anti-inflammatory effect of non-steroidal compounds on the eye, we tested them in rabbits using the inhibitory effect on paracentesis-induced disruption of the blood-aqueous barrier. Protein and--after intravenous-injection--fluorescein were determined in punctates of aqueous humor. Indomethacin, flurbiprofen and diclofenac in a 0.01% solution showed a marked inhibitory effect, which lasted for 24 h. Addition of polysorbate to eye drugs diminished the inhibitory effect.

Animals↗
PubMedDate not supplied

Parenteral nutrition hypersensitivity.

Total parenteral nutrition (TPN) is widely used. Although mechanical, septic, and metabolic complications are well known, hypersensitivity skin reactions are rare. We describe a 16-year-old boy with Burkitt's lymphoma who developed a urticarial skin rash when treated with TPN and vitamins. The adverse skin reaction was probably caused by the inactive component of excipient, polysorbate.

Adolescent↗
PubMed2004

Disposition kinetics of taxanes after intraperitoneal administration in rats and influence of surfactant vehicles.

Rats were intraperitoneally administered 40 mg x kg(-1) of paclitaxel or docetaxel dissolved in various drug solutions. The drug solutions were prepared using 20 mL of saline, adding 4.2% Cremophor EL (crEL) for paclitaxel (TXL), and 1.5% Polysorbate-80 (PS-80) (TXT), 7.5% PS-80 (TXT+PS-80) or 4.2% crEL (TXT+crEL) for docetaxel. The apparent first-order absorption rate constant from the peritoneal cavity (k(a)) of TXL was about one-twentieth of that of TXT. The ratio of the area under the concentration-time curve of drug in plasma over that in ascites for TXL was about one-third of that of TXT. The values of the above ratio and the k(a) of TXT+PS-80 and TXT+crEL were similar to those of TXL. After intraperitoneal administration, the values of the blood-to-plasma concentration ratio in the four groups were similar and independent of time. In the in-vitro study, PS-80 and crEL caused similar, concentration-dependent decreases of drug permeation into red blood cells after a 15-min incubation of rat blood with 10 microg x mL(-1) of TXL. We demonstrated that the disposition kinetics of taxanes after intraperitoneal administration to rats was strongly influenced, in a concentration-dependent manner, by the surfactant vehicle used, crEL or PS-80.

Animals↗